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SYSTEMATIC NAME

IUBMB Comments

ATP:protein-L-histidine N-phosphotransferase

This entry has been included to accommodate those protein-histidine kinases for which the phosphorylation site has not been established (i.e. either the pros- or tele-nitrogen of histidine). A number of histones can act as acceptor.

different structures of FimS kinase domains in strains strain ATCC 33277 and strain W83; different structures of FimS kinase domains in strains strain ATCC 33277 and strain W83. Although the production of FimR in W83 is modest, the protein still is detectable and can be functional because its amino acid sequence is almost identical to that of strain ATCC 33277, except for the alteration of one residue from serine to threonine, S209T

glycerol and manganese have a similar biofilm-promoting effect in two related Bacillus species, Bacillus licheniformis and Bacillus cereus, indicating that the biofilm-promoting effect of GM is conserved in Bacillus species

CheA differs from sensor histidine kinases in several ways: CheA does not contain a transmembrane domain, relying instead on P5 and CheW for interaction with transmembrane components. It has the phosphorylatable His residue on a separate domain (P1) instead of the dimerization domain (P3), and it utilizes a separate docking domain (P2) for CheY. P2 is not necessary for phosphotransfer to the response regulator CheY per se but variants lacking the P2 domain (DELTAP2) exhibit a reduced phosphotransfer rate relative to full-length CheA (CheAFL) and support a lower extent of chemotaxis. The linkers between the CheA domains play important roles in CheA activity

while the GacS/GacA two-component system is widely distributed throughout the bacterial kingdom, the molecular switch formed by the hybrid LadS, PA1611 and RetS histifine kinases is unique to the Pseudomonas species, though it can function in very different ways in phylogenetically related Pseudomonas species; while the GacS/GacA two-component system is widely distributed throughout the bacterial kingdom, the molecular switch formed by the hybrid LadS, PA1611 and RetS histifine kinases is unique to the Pseudomonas species, though it can function in very different ways in phylogenetically related Pseudomonas species

different structures of FimS kinase domains in strains strain ATCC 33277 and strain W83. Although the production of FimR in W83 is modest, the protein still is detectable and can be functional because its amino acid sequence is almost identical to that of strain ATCC 33277, except for the alteration of one residue from serine to threonine, S209T

HP0244 deletion abolishes urease activation and assembly, impairs cytoplasmic and periplasmic pH homeostasis, and depolarizes the cells, with an about 7-log loss of survival at pH 2.5, even in 10 mM urea

the wild-type strain experiences copper susceptibility at 2.75 mM CuSO4, whereas DELTAcusS mutant cells show a phenotype at lower concentrations. The growth defects observed in the DELTAcusS strain can be partially rescued by expression of intact CusS from a plasmid

residue 293 plays a central role in the altered structural specificity of the DELTA280-293 truncation, activation of VirA by phenols increases in the absence of enzyme aas 285-293. Mutations in the L domain can rescue null mutants in the R domain. Y293F substitution switches VirA from requiring two separate inputs to an OR gate, responding to both signals separately

in contrast to the wild-type strain, which forms mature pigmented perithecia, only an insignificant number of small unpigmented mutant fruiting bodies are observed in the dcc-1 deletion mutant, thus deletion of dcc-1 leads to sterility. Supplementation with cAMP does not restore the sexual defects (formation of submerged perithecia) of the DELTAdcc-1 mutant

impairment of the AaHSK1 gene does not reduce radial growth of the resulting two null mutants (HD1 and HD2) in the presence of tert-butyl-hydroxyperoxide, H2O2, KCl or NaCl, compared to the wild-type. Expression of a functional copy of the AaHSK1 gene in the HD1 null mutant fully restores the altered phenotypes. Deletion of AaHSK1 affects AaHOG1 phosphorylation. Fungal mutants impaired in AaHSK1, AaHOG1, AaAP1 (encoding a redox-responsive transcription factor) or AaFUS3 (encoding a MAP kinase) are all hypersensitive to 2-chloro-5-hydroxypyridine or 2,3,5-triiodobenzoic acid. Glucose enhances AaHOG1 phosphorylation and nuclear localization in the AaHSK1 deficient background. Genetic disruption of the AaHSK1 gene yields fungal strains that are insensitive to dicarboximide (iprodione and vinclozolin) and phenylpyrrole (fludioxonil) fungicides. Inactivation of the AaHSK1 or AaHOG1 gene does not alter the production of host-selective ACT toxin by Alternaria alternata

a group A streptococci strain selectively deficient in CovS phosphatase activity has a distinct transcriptome relative to that of its parental strain. Inactivation of CovS in the serotype M1 background results in a greater decrease in phosphorylated CovR levels and a greater increase in the transcript levels of CovR-repressed genes than does CovS inactivation in a serotype M3 strain

a group A streptococci strain selectively deficient in CovS phosphatase activity has a distinct transcriptome relative to that of its parental strain. Inactivation of CovS in the serotype M1 background results in a greater decrease in phosphorylated CovR levels and a greater increase in the transcript levels of CovR-repressed genes than does CovS inactivation in a serotype M3 strain

group B streptococci deficient in RgfC expression exhibit increased virulence, deletion of rgfC in group B streptococci strains lacking a functional RgfA increased systemic infection. Infection with the rgfC mutant increases induction of proinflammatory signaling pathways in vivo. 19 phosphopeptides corresponding to 12 proteins are differentially phosphorylated at aspartate, cysteine, serine, threonine, or tyrosine residues in the rgfC mutant. This includes aspartate phosphorylation of a tyrosine kinase, CpsD, and a transcriptional regulator. Over 200 genes show altered expression compared to the isogenic wild-type strain and included transcriptional regulators, transporters, and genes previously associated with group B streptococci pathogenesis. In the absence of RgfA, nonspecific RgfC signaling affects the expression of virulence factors and GBS pathogenesis. Sialic acid levels are higher in the DELTArgfCAd mutant than in wild-type A909, correlated with an increase in gene expression of the capsular polysaccharide operon. Sialylation of the group B streptococci capsular polysaccharide is critical for group B streptococci bloodstream infections and pathogenesis

the isogenic chiS mutant (ChiS-) shows less growth compared to the wild-type strain ChiS+ in the presence of mucin supplemented media. The mutant ChiS- strain also shows highly retarded motility as well as mucin layer penetration in vitro

enzyme FimS from W83 is malfunctional. Complementation analysis with chimeric fimS constructs reveals that W83 FimS has a defective kinase domain due to a truncated conserved G3 box motif that provides an ATP-binding pocket. The introduction of the functional fimS from strain ATCC 33277 restores the production, but not polymerization, of endogenous FimA subunits in W83. But even the fimbria-deficient strain W83 retains the ability to polymerize FimA from strain ATCC 33277, indicating the assembly of mature FimA by a primary structure-dependent mechanism. Strain ATCC 33277 FimS-induced W83 FimA is a mature polypeptide and is localized on the cell surface

the DELTAkinD mutant (and less significantly the DELTAkinC mutant) has the most defective phenotype, while all other kin kinase mutants are able to respond to the addition of GM by forming robust biofilm

DeltaHik34 mutant cells are resistant to heat stress within its first hours, they cannot recover after 24 h long high temperature treatment, while the wild-type cell population is able to recover after 24 h of cultivation at 44°C. The damage caused by high temperature depends on many factors, which differ in these experiments: light intensity, CO2 content, the growth stage, or the growth temperature before heat stress. In DELTAHik34 mutant, the content of all pigments starts to decrease after 6 h of heat stress. Heat stress phenotypes, overview

disruption of Shk1 results in resistance to phenylpyrrole and dicarboximide fungicides and increases sensitivity to hyperosmotic stress and H2O2-induced oxidative stress. The Shk1 mutant shows a significant reduction in vegetative hyphal growth and is unable to produce sclerotia. The Shk1 mutant shows no change in virulence. All the defects are restored by genetic complementation of the Shk1 deletion mutant with the wild-type Shk1 gene

loss of function of AHK5 also confers tolerance to high salinity, suggesting that AHK5 acts to integrate multiple stress responses. The AHK5 mutant is more resistant to salt stress, the insensitivity of the ahk5-1 mutant in response to salinity is caused by loss of AHK5 function

removal of the HAMP or the PAS domain from Hik33n-SphSc and substitutions of amino acid residues in the PAS domain influence kinase activity, overview. Subdomain-deleted variants of Hik33n-SphSc show reduced activity compared to the unaltered chimera; removal of the HAMP or the PAS domain from Hik33n-SphSc and substitutions of amino acid residues in the PAS domain influence kinase activity, overview. Subdomain-deleted variants of Hik33n-SphSc show reduced activity compared to the unaltered chimera

in the absence of LOVHK the expression of the virB operon is downregulated. LOVHK plays a role in the intracellular survival of Brucella, since deletion of this gene in Brucella abortus shows an attenuated phenotype in cell-culture infection assays. PhyR expression is decreased in the lovhk mutant

residue 293 plays a central role in the altered structural specificity of the DELTA280-293 truncation, activation of VirA by phenols increases in the absence of enzyme aas 285-293. Mutations in the L domain can rescue null mutants in the R domain. Y293F substitution switches VirA from requiring two separate inputs to an OR gate, responding to both signals separately

impairment of the AaHSK1 gene does not reduce radial growth of the resulting two null mutants (HD1 and HD2) in the presence of tert-butyl-hydroxyperoxide, H2O2, KCl or NaCl, compared to the wild-type. Expression of a functional copy of the AaHSK1 gene in the HD1 null mutant fully restores the altered phenotypes. Deletion of AaHSK1 affects AaHOG1 phosphorylation. Fungal mutants impaired in AaHSK1, AaHOG1, AaAP1 (encoding a redox-responsive transcription factor) or AaFUS3 (encoding a MAP kinase) are all hypersensitive to 2-chloro-5-hydroxypyridine or 2,3,5-triiodobenzoic acid. Glucose enhances AaHOG1 phosphorylation and nuclear localization in the AaHSK1 deficient background. Genetic disruption of the AaHSK1 gene yields fungal strains that are insensitive to dicarboximide (iprodione and vinclozolin) and phenylpyrrole (fludioxonil) fungicides. Inactivation of the AaHSK1 or AaHOG1 gene does not alter the production of host-selective ACT toxin by Alternaria alternata

N-terminal truncations of YycG lose negative regulation of their activity, phenotypes, overview. Truncated YycG constructs fail to co-immunoprecipitate with the regulatory proteins YycH and YycI. Deletion or depletion of later stage cell division proteins does not perturb YycG localization; the DELTAkinD mutant (and less significantly the DELTAkinC mutant) has the most defective phenotype, while all other kin kinase mutants are able to respond to the addition of GM by forming robust biofilm

in the absence of LOVHK the expression of the virB operon is downregulated. LOVHK plays a role in the intracellular survival of Brucella, since deletion of this gene in Brucella abortus shows an attenuated phenotype in cell-culture infection assays. PhyR expression is decreased in the lovhk mutant

in contrast to the wild-type strain, which forms mature pigmented perithecia, only an insignificant number of small unpigmented mutant fruiting bodies are observed in the dcc-1 deletion mutant, thus deletion of dcc-1 leads to sterility. Supplementation with cAMP does not restore the sexual defects (formation of submerged perithecia) of the DELTAdcc-1 mutant

enzyme FimS from W83 is malfunctional. Complementation analysis with chimeric fimS constructs reveals that W83 FimS has a defective kinase domain due to a truncated conserved G3 box motif that provides an ATP-binding pocket. The introduction of the functional fimS from strain ATCC 33277 restores the production, but not polymerization, of endogenous FimA subunits in W83. But even the fimbria-deficient strain W83 retains the ability to polymerize FimA from strain ATCC 33277, indicating the assembly of mature FimA by a primary structure-dependent mechanism. Strain ATCC 33277 FimS-induced W83 FimA is a mature polypeptide and is localized on the cell surface

disruption of Shk1 results in resistance to phenylpyrrole and dicarboximide fungicides and increases sensitivity to hyperosmotic stress and H2O2-induced oxidative stress. The Shk1 mutant shows a significant reduction in vegetative hyphal growth and is unable to produce sclerotia. The Shk1 mutant shows no change in virulence. All the defects are restored by genetic complementation of the Shk1 deletion mutant with the wild-type Shk1 gene

the isogenic chiS mutant (ChiS-) shows less growth compared to the wild-type strain ChiS+ in the presence of mucin supplemented media. The mutant ChiS- strain also shows highly retarded motility as well as mucin layer penetration in vitro

compared to a serotype M3 strain, serotype M1 GAS strains have high levels of phosphorylated CovR, low transcript levels of CovR-repressed genes, and strikingly different responses to environmental cues. Genetic inactivation of covS decreases but does not eliminate CovR phosphorylation

biofilm formation depends on the synthesis of an extracellular matrix, which is indirectly regulated by the transcriptional regulator Spo0A. The activity of Spo0A depends on its phosphorylation state. Low and intermediate levels of phosphorylated Spo0A lead to induction of the epsA-O and tapA operons, which results in production of the extracellular matrix and thus biofilm formation, while at high levels, the matrix genes are repressed. The level of phosphorylated Spo0A is controlled by a network of kinases and phosphatases, which respond to environmental and physiological signals. Biofilm formation of Bacillus subtilis in LB medium is triggered by a combination of glycerol and manganese via KinD sensoring. The kinase KinD contains an extracellular domain, so called CACHE domain, for sensing small chemical molecules released from plant host during colonization. The glpK-encoded glycerol kinase and glpF encoded glycerol transport facilitator are critical in utilization of glycerol as a carbon source; five distinct sensor kinases (KinA, KinB, KinC, KinD, and KinE) have the capability of transferring a phosphoryl group into the phosphorelay to control the level of phosphorylated transcriptional regulator Spo0A present at any moment in the cell

in response to starvation, Bacillus subtilis cells differentiate into different subsets, undergoing cannibalism, biofilm formation or sporulation. These processes require a multiple component phosphorelay, wherein the master regulator Spo0A is activated upon phosphorylation by one or a combination of five histidine kinases (KinA-KinE) via two intermediate phosphotransferases, Spo0F and Spo0B. KinC controls the expression of cannibalism genes in a manner independent of surfactin andthe bacterial flotillin-like proteins FloT and FloA

biofilm formation depends on the synthesis of an extracellular matrix, which is indirectly regulated by the transcriptional regulator Spo0A. The activity of Spo0A depends on its phosphorylation state. Low and intermediate levels of phosphorylated Spo0A lead to induction of the epsA-O and tapA operons, which results in production of the extracellular matrix and thus biofilm formation, while at high levels, the matrix genes are repressed. The level of phosphorylated Spo0A is controlled by a network of kinases and phosphatases, which respond to environmental and physiological signals. Biofilm formation of Bacillus subtilis in LB medium is triggered by a combination of glycerol and manganese via KinD sensoring. The kinase KinD contains an extracellular domain, so called CACHE domain, for sensing small chemical molecules released from plant host during colonization. The glpK-encoded glycerol kinase and glpF encoded glycerol transport facilitator are critical in utilization of glycerol as a carbon source; five distinct sensor kinases (KinA, KinB, KinC, KinD, and KinE) have the capability of transferring a phosphoryl group into the phosphorelay to control the level of phosphorylated transcriptional regulator Spo0A present at any moment in the cell; in response to starvation, Bacillus subtilis cells differentiate into different subsets, undergoing cannibalism, biofilm formation or sporulation. These processes require a multiple component phosphorelay, wherein the master regulator Spo0A is activated upon phosphorylation by one or a combination of five histidine kinases (KinA-KinE) via two intermediate phosphotransferases, Spo0F and Spo0B. KinC controls the expression of cannibalism genes in a manner independent of surfactin andthe bacterial flotillin-like proteins FloT and FloA

the VirA receiver domain is required for efficient vir gene expression, including the transcriptional induction of virG, VirA's receiver domain acts as a recruitment and/or alignment factor that increases the availability of VirG for phosphate transfer from VirA's kinase region to the VirG receiver domain

cytokinin-independent1 and Arabidopsis histidine kinase2 and 3 regulate vascular tissue development in Arabidopsis shoots, the cytokinin-independent activity of CKI1 and cytokinin-induced histidine kinase2 and histidine kinase3 are important for vascular bundle formation in Arabidopsis

the DraR/DraK two-component system (TCS) of Streptomyces coelicolor is involved in the differential regulation of antibiotic biosynthesis. The extracellular sensory domain of histidine kinase DraK shows a pH-dependent conformational change involved in signal transduction process of DraR/DraK TCS. At low pH, the extracellular sensory domain is more structured than that at high pH. In particular, the glutamate at position 83 is an important residue for the pH-dependent conformational change

the globin-coupled histidine kinase, AfGcHK, is a part of the two-component signal transduction system. Activation of its sensor domain significantly increases its autophosphorylation activity, which targets the His183 residue of its functional domain. The phosphate group of phosphorylated AfGcHK is then transferred to the cognate response regulator

in bacteria, two-component systems act as signaling systems to respond to environmental stimuli. Two-component systems generally consist of a sensor histidine kinase and a response regulator, which work together through histidyl-aspartyl phospho-relay to result in gene regulation. One of the two-component systems in Escherichia coli, CusS-CusR, is known to induce expression of cusCFBA genes under increased periplasmic Cu(I) and Ag(I) concentrations to help maintain metal ion homeostasis. CusS senses increasing metal ion concentrations and activates CusR. ATP-dependent auto-phosphorylation occurs at a conserved His residue in the kinase core. The phosphoryl group is then transferred from the histidine kinase to a conserved Asp residue on the N-terminal receiver domain of the response regulator, which in turn activates the C-terminal effector domain to mediate an adaptive response. The phosphorylated response regulator activates transcription of genes that respond to the environmental stimulus. Analysis of the molecular role of CusS in Cu(I)/Ag(I) resistance and the mechanism of CusS signal transduction in Escherichia coli, overview. In response to periplasmic Ag(I) and Cu(I), CusS upregulates the genes to express the CusCBA Cu(I)/Ag(I) efflux pump to remove excess metal ions from the cell

CusS is a prototypical periplasmic sensing histidine kinase, the histidine kinase CusS of the CusRS two-component system functions as a Ag(I)/Cu(I)-responsive sensor kinase and is essential for induction of the genes encoding the CusCFBA efflux pump. CusS has an important role in silver resistance and regulation of copper homeostasis

Ti plasmid-encoded two-component signaling system, designated VirA and VirG, where VirA serves as the histidine autokinase antenna that phosphorylates VirG as the active transcriptional regulator. Histidine kinase VirA processes multiple small molecule host signals (phenol and sugar) and is essential for pathogenesis of Rhizobium radiobacter. A single residue can switch enzyme VirA from a functional AND logic gate to an OR gate where each of two signals activate independently. Host range preferences among natural strains of Rhizobium radiobacter correlate with these gate logic strategies. VirA, which exists in the inner membrane as a homodimer, is composed of multiple domains assigned as periplasmic (P), linker (L), kinase (K), and receiver (R). Sugar perception requires the P domain, whereas phenols require the L domain, localizing detection of these small molecules to opposite sides of the inner membrane. Importance of the integration node, specifically residue 293, as critical for signaling. In most natural isolates, including the frequently used A6 and C58 strains, the wild-type residue for 293 is tyrosine, but in strains Ag162, AB2/73, and KU12, the residue at 293 is phenylalanine. Strains A6, C58, and KU12 are wide-host-range pathogens, whereas strains Ag162 and AB2/73 show limited host ranges

Arabidopsis thaliana endosperm formation requires the cytokinin independent 1 (CKI1) histidine kinase, an activator of the cytokinin signaling pathway, which specifies central cells and restricts egg cell fate. Seeds of flowering plants contain embryos and nutritive endosperm arising from double fertilization of two dimorphic female gametes. The key to specification of only one female gamete for endosperm formation is the regulated localization of the CKI1 histidine kinase by expression control and protein translocation. Dimorphism of the two adjacent gametes is mechanistically established in the syncytial embryo sac by spatially restricted CKI1 expression, followed by translocation of endoplasmic reticulum-localized CKI1 protein via nuclear migration. CKI1-directed specification of the endosperm precursor central cell results in seeds containing an embryo and an endosperm, mechanism, overview

two-component signaling pathways are based on phosphoryl group transfer between histidine kinase and response regulator proteins and regulate environmental responses. The DCC-1 protein in Neurospora crasse protein participates in the regulation of processes such as conidiation, perithecial development, and, to a certain degree, carotenogenesis. DCC-1 exerts its effect by promoting cyclic AMP production, including GNA-3 and CR-1, thereby placing this protein within the context of a signaling pathway that operates during conidiation and sexual development. The DCC-1 histidine kinase is required for proper perithecial development, it has a significant role as a negative regulator of sporulation during vegetative growth

Hik2 is the cytoplasmic homologue of chloroplast sensor kinase (CSK), a protein involved in redox regulation of chloroplast gene expression during changes in light quality in plants and algae. Hik2 is the sensor that acts on Rre1 and RppA transcription factors to regulate photosynthesis genes as part of the mechanism of photosystem stoichiometry adjustment in cyanobacteria. Signaling mechanism of Hik2 and its phosphotransferase activity, overview. Hik2-based signaling pathway integrates acclimatory responses to light and salt stresses in cyanobacteria

AaHSK1 is a primary regulator for cellular resistance to sugar osmotic stress and for sensitivity to dicarboximide or phenylpyrrole fungicides. Important role of AaHSK1 in osmotic adaption, specifically to sugar osmoticants. AaHSK1 does not play an essential role in fungal pathogenicity

two-component gene regulatory systems (TCSs) are a major mechanism by which bacteria respond to environmental stimuli and are critical to infectivity. The control of virulence regulator/sensor kinase (CovRS) TCS is central to the virulence of the major human pathogen group A Streptococcus (GAS). In the system, the histidine kinase CovS primarily serves to phosphorylate CovR, thereby resulting in the repression of virulence factor-encoding genes. Both CovS kinase and phosphatase activities influence the CovR phosphorylation status. Serotype M1 GAS strains have high rates of spontaneous mutations in covS during invasive GAS infection, thus providing a link between TCS molecular function and the epidemiology of deadly bacterial infections

two-component gene regulatory systems (TCSs) are a major mechanism by which bacteria respond to environmental stimuli and are critical to infectivity. The control of virulence regulator/sensor kinase (CovRS) TCS is central to the virulence of the major human pathogen group A Streptococcus (GAS). In the system, the histidine kinase CovS primarily serves to phosphorylate CovR, thereby resulting in the repression of virulence factor-encoding genes. Both CovS kinase and phosphatase activities influence the CovR phosphorylation status. Serotype M1 GAS strains have high rates of spontaneous mutations in covS during invasive GAS infection, thus providing a link between TCS molecular function and the epidemiology of deadly bacterial infections

role of a sensor histidine kinase ChiS as an regulator in pathogenesis. The enzyme regulates the chitin utilization pathway and the associated two required factors, chitin binding protein and chitinases, like ChiA2. Enzyme ChiS is important for adherence and survival in HT-29 cells. ChiS is an important factor for utilizing mucin as a sole nutrient source. Cell adhesion, motility, and mucin penetration depends on ChiS. ChiS affects suckling mice colonization in mice and contributes in fluid accumulation as well as colonization in rabbit intestine

the FimA-related gene cluster (the fim gene cluster) is positively regulated by the FimS-FimR two-component system. The assembly of mature FimA by a primary structure-dependent mechanism. FimSR is the unique and universal regulatory system that activates the fim gene cluster in a fimA genotype-independent manner

KinD is a principal histidine kinase for sensing the presence of GM, exclusively by its extracellular CACHE domain. A combination of glycerol and manganese promotes multicellular development by Bacillus subtilis. The strong biofilm-stimulating activity in response to the addition of a combination of glycerol and manganese is indeed due to upregulation of the matrix genes mediated mainly by the histidine kinase KinD; the activity of transcriptional regulator Spo0A depends on its phosphorylation state. The level of phosphorylated Spo0A is controlled by a network of kinases and phosphatases, which respond to environmental and physiological signals. KinD is a principal histidine kinase responsible for sensing the presence of glycerol and manganese, which trigger biofilm formation of Bacillus subtilis in LB medium, exclusively by its extracellular CACHE sensor domain. The biofilm-promoting effect of glycerol and manganese is mediated mainly by the histidine kinase KinD

two-component signal transduction systems (TCSs) in bacteria perceive environmental stress and transmit the information via phosphorelay to adjust multiple cellular functions for adaptation. The EvgS/EvgA system is a TCS that confers acid resistance to Escherichia coli cells. Activation of the EvgS sensor initiates a cascade of transcription factors, EvgA, YdeO, and GadE, which induce the expression of a large group of acid resistance genes

gene VF_A0360 encodes the biofilm inhibitor kinase binK, an orphan hybrid histidine kinase that negatively regulates the Vibrio fischeri symbiotic biofilm (Syp) in vivo and in vitro. Colonization of Euprymna scolopes bobtail squid by Vibrio fischeri bacteria requires bacterial aggregation in host mucus as the symbiont transitions from a planktonic lifestyle in seawater to a biofilm-associated state in the host. Enzyme BinK acts upstream of SypG, the sigma54-dependent transcriptional regulator of the syp biofilm locus. The BinK effects are dependent on intact signaling in the RscS-Syp biofilm pathway. Enzyme BinK antagonizes the signal from RscS and serves as an integral component in Vibrio fischeri biofilm regulation. The hybrid histidine kinase BinK is a negative regulator of in vivo aggregation and squid colonization and of Syp biofilm phenotypes in culture. BinK is acting through SypG and not SypE

DesK is a sensor histidine kinase that allows Bacillus subtilis to respond to cold shock, triggering the adaptation of membrane fluidity via transcriptional control of a fatty acid desaturase. The transmembrane region can sense temperature-modulated fluidity changes of lipid bilayers, transmitting the signal toward the C-terminal cytoplasmic catalytic core of about 220 residues. The cold thermal stimulus is detected by DesK, which then interacts with its cognate response regulator, DesR, constituting a canonical two-component system, TCS

CheA differs from sensor histidine kinases in several ways: CheA does not contain a transmembrane domain, relying instead on P5 and CheW for interaction with transmembrane components. It has the phosphorylatable His residue on a separate domain (P1) instead of the dimerization domain (P3), and it utilizes a separate docking domain (P2) for CheY. P2 is not necessary for phosphotransfer to the response regulator CheY per se but variants lacking the P2 domain (DELTAP2) exhibit a reduced phosphotransfer rate relative to full-length CheA (CheAFL) and support a lower extent of chemotaxis. The linkers between the CheA domains play important roles in CheA activity

the enzyme Hik34 plays an important role in changes in transcriptome, proteome, lipidome, and photosynthesis in response to short term heat stress. Hik34 affects the expression of sets of genes under salt and osmotic stress, under normal conditions and heat stress and under oxidative stress

enzyme KinC regulates cannibalism and biofilm formation, and activates the expression of cannibalism genes in response to starvation in a manner dependent on phosphorelay. KinC activity and the membrane localization are independent of both the lipid raft marker proteins FloTA and cytoplasmic potassium concentration. KinC becomes active by forming a homotetramer via the N-terminal PAS domain

The enzyme YycG is part of the two-component signal transduction system YycFG or WalRK. The YycG (WalK) sensor histidine kinase coordinates cell wall remodeling with cell division in Gram-positive bacteria by controlling the transcription of genes for autolysins and their inhibitors. The essential enzyme YycG senses cell division and is enzymatically activated by associating with the divisome at the division septum. The cytoplasmic PAS domain of this multidomain trans-membrane kinase is a determining factor translocating the kinase to the division septum. YycG activity in non-dividing cells is suppressed by its interaction with YycH and YycI and its activation is coordinated to cell division in dividing cells by specific interactions that occur within the divisome. This regulation is accomplished through its transmembrane and extra-membrane domains interacting with the membrane associated YycH and YycI proteins that do not localize to the divisome. Signaling by YycG involves later stage cell division proteins, overview

the hybrid histidine kinase Arabidopsis histidine kinase 5 (AHK5) mediates stomatal responses to exogenous and endogenous signals in Arabidopsis thaliana, AHK5 integrates abiotic and biotic stimuli in stomatal guard cells through regulation of H2O2 homeostasis. Role for AHK5 in the regulation of survival following challenge by a hemi-biotrophic bacterium and a necrotrophic fungus, as well as in the growth response to salt stress. AHK5 positively regulates salt sensitivity and contributes to resistance to the bacterium Pseudomonas syringae pv. tomato DC3000 and the fungal pathogen Botrytis cinerea, detailed overview. Function of AHK5 in regulating the production of hormones and redox homeostasis. Enzyme AHK5 functions as a negative regulator of root growth inhibition mediated by abscisic acid/ethylene. AHK5 positively regulates salt-induced root growth inhibition

histidine kinase Hik33 is one of the key regulators helping Synechocystis acclimate to multiple stress conditions, Hik33 may play important roles in allowing cells to acclimate to changing environmental conditions; histidine kinase SphS senses phosphate-deficient conditions. SphS phosphorylates its cognate response regulator, SphR, under phosphate-deficient conditions and regulates the expression of the so-called pho regulon, which includes genes for acclimation to phosphate-deficient conditions, namely genes for a periplasmic alkaline phosphatase PhoA and phosphate transporters

one of the main components of two-component systems, TCSs, is a sensor histidine kinase, which relays extracellular signals to intracellular pathways. VicK is an important sensor histidine kinase in the tooth decay pathogen Streptomyces mutans

in response to environmental changes, Pseudomonas aeruginosa is able to switch from a planktonic (free swimming) to a sessile (biofilm) lifestyle. The two-component system GacS/GacA activates the production of two small non-coding RNAs, RsmY and RsmZ, but four histidine kinases, RetS, GacS, LadS and PA1611, are instrumental in this process. RetS hybrid histidine kinase blocks GacS unorthodox histidine kinase autophosphorylation through the formation of a heterodimer. PA1611 hybrid histidine kinase, which is structurally related to GacS, interacts with RetS in Pseudomonas aeruginosa in a very similar manner to GacS. LadS hybrid histidine kinase phenotypically antagonizes the function of RetS by a mechanism that has never been investigated. The four sensors are found in most Pseudomonas species but their characteristics and mode of signaling may differ from one species to another. In Pseudomonas aeruginosa, LadS controls both rsmY and rsmZ gene expression and this regulation occurs through the GacS/GacA two-component system. In contrast to RetS, LadS signals through GacS/GacA without forming heterodimers, either with GacS or with RetS. Enzyme LadS is involved in a genuine phospho relay, which requires both transmitter and receiver LadS domains. LadS signaling ultimately requires the alternative histidine-phosphotransfer domain of GacS. LadS histidine kinase forms, with the GacS/GacA two-component system, a multicomponent signal transduction system with an original phosphorelay cascade, i.e. H1LadS -> D1LadS -> H2GacS -> D2GacA. This highlights an original strategy in which a unique output, i.e. the modulation of sRNA levels, is controlled by a complex multi-sensing network to fine-tune an adapted biofilm and virulence response. H1 and D1 domain involvement of the LadS hybrid histidine kinase in the LadS signaling pathway, and involvement of the H2 domain of the GacS unorthodox histidine kinase in the LadS signaling pathway, overview; in response to environmental changes, Pseudomonas aeruginosa is able to switch from a planktonic (free swimming) to a sessile (biofilm) lifestyle. The two-component system GacS/GacA activates the production of two small non-coding RNAs, RsmY and RsmZ, but four histidine kinases, RetS, GacS, LadS and PA1611, are instrumental in this process. RetS hybrid histidine kinase blocks GacS unorthodox histidine kinase autophosphorylation through the formation of a heterodimer. PA1611 hybrid histidine kinase, which is structurally related to GacS, interacts with RetS in Pseudomonas aeruginosa in a very similar manner to GacS. LadS hybrid histidine kinase phenotypically antagonizes the function of RetS. The four sensors are found in most Pseudomonas species but their characteristics and mode of signaling may differ from one species to another. In Pseudomonas aeruginosa, LadS controls both rsmY and rsmZ gene expression and this regulation occurs through the GacS/GacA two-component system. In contrast to RetS, LadS signals through GacS/GacA without forming heterodimers, either with GacS or with RetS. Enzyme LadS is involved in a genuine phospho relay, which requires both transmitter and receiver LadS domains. LadS signaling ultimately requires the alternative histidine-phosphotransfer domain of GacS. LadS histidine kinase forms, with the GacS/GacA two-component system, a multicomponent signal transduction system with an original phosphorelay cascade, i.e. H1LadS -> D1LadS -> H2GacS -> D2GacA. This highlights an original strategy in which a unique output, i.e. the modulation of sRNA levels, is controlled by a complex multi-sensing network to fine-tune an adapted biofilm and virulence response. In vitro transphosphorylation of GacS H2 domain by LadS histidine kinase, involvement of the H2 domain of the GacS unorthodox histidine kinase in the LadS signaling pathway

LOV histidine kinase positively regulates the general stress response system and affects the virB operon expression in Brucella abortus. The Brucella genome encodes a sensor histidine kinase containing a LOV domain upstream from the kinase, LOVHK, which plays an important role in light-regulated Brucella virulence. The intracellular signaling pathway is initiated by the light sensor LOVHK, which functionally interacts with two response regulators: PhyR and LovR, constituting a functional two-component signal-transduction system. LOVHK contributes to the activation of the general stress response (GSR) system in Brucella via PhyR, the main regulator of the general stress response system, while LovR is proposed to be a phosphate-sink for LOVHK, decreasing its phosphorylation state. LOVHK plays a role in the intracellular survival of Brucella and in defense of stress induced by starvation. LOVHK signaling cascade, overview

the DraR/DraK two-component system is involved in the differential regulation of antibiotic biosynthesis in a medium-dependent manner, the DraR/DraK two-component system plays an important role in the pH regulation of Streptomyces coelicolor growth medium. The enzyme and the DraR/DraK two-component system are essential for the recovery of the pH of Streptomyces coelicolor growth medium after acid shock, overview

Ti plasmid-encoded two-component signaling system, designated VirA and VirG, where VirA serves as the histidine autokinase antenna that phosphorylates VirG as the active transcriptional regulator. Histidine kinase VirA processes multiple small molecule host signals (phenol and sugar) and is essential for pathogenesis of Rhizobium radiobacter. A single residue can switch enzyme VirA from a functional AND logic gate to an OR gate where each of two signals activate independently. Host range preferences among natural strains of Rhizobium radiobacter correlate with these gate logic strategies. VirA, which exists in the inner membrane as a homodimer, is composed of multiple domains assigned as periplasmic (P), linker (L), kinase (K), and receiver (R). Sugar perception requires the P domain, whereas phenols require the L domain, localizing detection of these small molecules to opposite sides of the inner membrane. Importance of the integration node, specifically residue 293, as critical for signaling. In most natural isolates, including the frequently used A6 and C58 strains, the wild-type residue for 293 is tyrosine, but in strains Ag162, AB2/73, and KU12, the residue at 293 is phenylalanine. Strains A6, C58, and KU12 are wide-host-range pathogens, whereas strains Ag162 and AB2/73 show limited host ranges

gene VF_A0360 encodes the biofilm inhibitor kinase binK, an orphan hybrid histidine kinase that negatively regulates the Vibrio fischeri symbiotic biofilm (Syp) in vivo and in vitro. Colonization of Euprymna scolopes bobtail squid by Vibrio fischeri bacteria requires bacterial aggregation in host mucus as the symbiont transitions from a planktonic lifestyle in seawater to a biofilm-associated state in the host. Enzyme BinK acts upstream of SypG, the sigma54-dependent transcriptional regulator of the syp biofilm locus. The BinK effects are dependent on intact signaling in the RscS-Syp biofilm pathway. Enzyme BinK antagonizes the signal from RscS and serves as an integral component in Vibrio fischeri biofilm regulation. The hybrid histidine kinase BinK is a negative regulator of in vivo aggregation and squid colonization and of Syp biofilm phenotypes in culture. BinK is acting through SypG and not SypE

AaHSK1 is a primary regulator for cellular resistance to sugar osmotic stress and for sensitivity to dicarboximide or phenylpyrrole fungicides. Important role of AaHSK1 in osmotic adaption, specifically to sugar osmoticants. AaHSK1 does not play an essential role in fungal pathogenicity

the globin-coupled histidine kinase, AfGcHK, is a part of the two-component signal transduction system. Activation of its sensor domain significantly increases its autophosphorylation activity, which targets the His183 residue of its functional domain. The phosphate group of phosphorylated AfGcHK is then transferred to the cognate response regulator

Arabidopsis thaliana endosperm formation requires the cytokinin independent 1 (CKI1) histidine kinase, an activator of the cytokinin signaling pathway, which specifies central cells and restricts egg cell fate. Seeds of flowering plants contain embryos and nutritive endosperm arising from double fertilization of two dimorphic female gametes. The key to specification of only one female gamete for endosperm formation is the regulated localization of the CKI1 histidine kinase by expression control and protein translocation. Dimorphism of the two adjacent gametes is mechanistically established in the syncytial embryo sac by spatially restricted CKI1 expression, followed by translocation of endoplasmic reticulum-localized CKI1 protein via nuclear migration. CKI1-directed specification of the endosperm precursor central cell results in seeds containing an embryo and an endosperm, mechanism, overview; cytokinin signaling is mediated by a multiple-step phosphorelay. Key components of the phosphorelay consist of the histidine kinase (HK)-type receptors, histidine phosphotransfer proteins (HP), and response regulators (RRs). Histidine kinase CKI1 acts upstream of histidine phosphotransfer proteins to regulate female gametophyte development and vegetative growth, role of AHP proteins in female gametophyte development, overview; the hybrid histidine kinase Arabidopsis histidine kinase 5 (AHK5) mediates stomatal responses to exogenous and endogenous signals in Arabidopsis thaliana, AHK5 integrates abiotic and biotic stimuli in stomatal guard cells through regulation of H2O2 homeostasis. Role for AHK5 in the regulation of survival following challenge by a hemi-biotrophic bacterium and a necrotrophic fungus, as well as in the growth response to salt stress. AHK5 positively regulates salt sensitivity and contributes to resistance to the bacterium Pseudomonas syringae pv. tomato DC3000 and the fungal pathogen Botrytis cinerea, detailed overview. Function of AHK5 in regulating the production of hormones and redox homeostasis. Enzyme AHK5 functions as a negative regulator of root growth inhibition mediated by abscisic acid/ethylene. AHK5 positively regulates salt-induced root growth inhibition

DesK is a sensor histidine kinase that allows Bacillus subtilis to respond to cold shock, triggering the adaptation of membrane fluidity via transcriptional control of a fatty acid desaturase. The transmembrane region can sense temperature-modulated fluidity changes of lipid bilayers, transmitting the signal toward the C-terminal cytoplasmic catalytic core of about 220 residues. The cold thermal stimulus is detected by DesK, which then interacts with its cognate response regulator, DesR, constituting a canonical two-component system, TCS; enzyme KinC regulates cannibalism and biofilm formation, and activates the expression of cannibalism genes in response to starvation in a manner dependent on phosphorelay. KinC activity and the membrane localization are independent of both the lipid raft marker proteins FloTA and cytoplasmic potassium concentration. KinC becomes active by forming a homotetramer via the N-terminal PAS domain; KinD is a principal histidine kinase for sensing the presence of GM, exclusively by its extracellular CACHE domain. A combination of glycerol and manganese promotes multicellular development by Bacillus subtilis. The strong biofilm-stimulating activity in response to the addition of a combination of glycerol and manganese is indeed due to upregulation of the matrix genes mediated mainly by the histidine kinase KinD; the activity of transcriptional regulator Spo0A depends on its phosphorylation state. The level of phosphorylated Spo0A is controlled by a network of kinases and phosphatases, which respond to environmental and physiological signals. KinD is a principal histidine kinase responsible for sensing the presence of glycerol and manganese, which trigger biofilm formation of Bacillus subtilis in LB medium, exclusively by its extracellular CACHE sensor domain. The biofilm-promoting effect of glycerol and manganese is mediated mainly by the histidine kinase KinD; The enzyme YycG is part of the two-component signal transduction system YycFG or WalRK. The YycG (WalK) sensor histidine kinase coordinates cell wall remodeling with cell division in Gram-positive bacteria by controlling the transcription of genes for autolysins and their inhibitors. The essential enzyme YycG senses cell division and is enzymatically activated by associating with the divisome at the division septum. The cytoplasmic PAS domain of this multidomain trans-membrane kinase is a determining factor translocating the kinase to the division septum. YycG activity in non-dividing cells is suppressed by its interaction with YycH and YycI and its activation is coordinated to cell division in dividing cells by specific interactions that occur within the divisome. This regulation is accomplished through its transmembrane and extra-membrane domains interacting with the membrane associated YycH and YycI proteins that do not localize to the divisome. Signaling by YycG involves later stage cell division proteins, overview

LOV histidine kinase positively regulates the general stress response system and affects the virB operon expression in Brucella abortus. The Brucella genome encodes a sensor histidine kinase containing a LOV domain upstream from the kinase, LOVHK, which plays an important role in light-regulated Brucella virulence. The intracellular signaling pathway is initiated by the light sensor LOVHK, which functionally interacts with two response regulators: PhyR and LovR, constituting a functional two-component signal-transduction system. LOVHK contributes to the activation of the general stress response (GSR) system in Brucella via PhyR, the main regulator of the general stress response system, while LovR is proposed to be a phosphate-sink for LOVHK, decreasing its phosphorylation state. LOVHK plays a role in the intracellular survival of Brucella and in defense of stress induced by starvation. LOVHK signaling cascade, overview

two-component signaling pathways are based on phosphoryl group transfer between histidine kinase and response regulator proteins and regulate environmental responses. The DCC-1 protein in Neurospora crasse protein participates in the regulation of processes such as conidiation, perithecial development, and, to a certain degree, carotenogenesis. DCC-1 exerts its effect by promoting cyclic AMP production, including GNA-3 and CR-1, thereby placing this protein within the context of a signaling pathway that operates during conidiation and sexual development. The DCC-1 histidine kinase is required for proper perithecial development, it has a significant role as a negative regulator of sporulation during vegetative growth

the FimA-related gene cluster (the fim gene cluster) is positively regulated by the FimS-FimR two-component system. The assembly of mature FimA by a primary structure-dependent mechanism. FimSR is the unique and universal regulatory system that activates the fim gene cluster in a fimA genotype-independent manner

one of the main components of two-component systems, TCSs, is a sensor histidine kinase, which relays extracellular signals to intracellular pathways. VicK is an important sensor histidine kinase in the tooth decay pathogen Streptomyces mutans

the DraR/DraK two-component system (TCS) of Streptomyces coelicolor is involved in the differential regulation of antibiotic biosynthesis. The extracellular sensory domain of histidine kinase DraK shows a pH-dependent conformational change involved in signal transduction process of DraR/DraK TCS. At low pH, the extracellular sensory domain is more structured than that at high pH. In particular, the glutamate at position 83 is an important residue for the pH-dependent conformational change

the DraR/DraK two-component system is involved in the differential regulation of antibiotic biosynthesis in a medium-dependent manner, the DraR/DraK two-component system plays an important role in the pH regulation of Streptomyces coelicolor growth medium. The enzyme and the DraR/DraK two-component system are essential for the recovery of the pH of Streptomyces coelicolor growth medium after acid shock, overview

role of a sensor histidine kinase ChiS as an regulator in pathogenesis. The enzyme regulates the chitin utilization pathway and the associated two required factors, chitin binding protein and chitinases, like ChiA2. Enzyme ChiS is important for adherence and survival in HT-29 cells. ChiS is an important factor for utilizing mucin as a sole nutrient source. Cell adhesion, motility, and mucin penetration depends on ChiS. ChiS affects suckling mice colonization in mice and contributes in fluid accumulation as well as colonization in rabbit intestine

effect of the nonconserved flanking sequence on the signaling lifetime of LovK, the effects of structure outside the LOV core on its signaling lifetime do not combine in a simple, additive way. Kinetics of recovery from the adduct state depend not only on the buffer environment but also on the structural context in which the LOV domain is contained. Full-length LovK (residues 1-368) has a long recovery, with a half-life of 2 h, the isolated LOV core (residues 25-138) recovers more quickly, with a half-life of 37 min. LovK (25-163), which contains the LOV core and the nonconserved linker sequence at its C-terminus, has a recovery half-life of 28 min. A construct containing the LOV core and the nonconserved N-terminal flanking sequence, LovK(1-138), has a half-life of only 2 min, but this N-terminal region has not a general rate enhancement effect. LovK(1-163), a construct with fully intact N- and C-termini (but missing the kinase domain), is slower to recover than either LovK(25-138), LovK(1-138), or LovK(25-163)

the coordination and oxidation state of the sensor domain heme iron profoundly affect the enzyme's catalytic activity because they modulate its ATP binding affinity and thus change its kcat/Km(ATP) value. Effects of the response regulator and different divalent metal cations on the autophosphorylation reaction, overview

the periplasmic sensor domain of CusS directly interacts with Ag(I) ions and undergoes a conformational change upon metal binding. Metal binding also enhances the tendency of the domain to dimerize. For NMR structure analysis, the enzyme is prepared with Ag+, Ni2+, Zn2+, and Cu+ ions via dialysis

basic architecture of VirA/VirG histidine kinase: the membrane-embedded VirA histidine kinase contains four modular domains, and the signal inputs activate the VirG response regulator. The sugar-binding protein ChvE interacts with the periplasmic domain, and phenols interact with the linker domain. The linker is predicted to adopt a GAF fold with the alpha1 helix. The conserved His474 is located in the dimerization domain of the kinase

KinD is located upstream of Spo0A and AbrB in the pathway. CACHE is present in many bacterial sensory histidine kinases and is capable of sensing small molecules, often in the presence of cofactors, such as metal ions

EvgS is a hybrid histidine kinase composed of a histidine kinase domain, receiver domain, and Hpt transmitter domain. The phosphate at the initial histidine residue in the histidine kinase domain is subsequently transferred to an aspartate residue in the receiver domain and is relayed to the second histidine residue in the Hpt domain before being transferred to the aspartate residue in EvgA

protein-protein docking analysis of the catalytic domain with the dimerization DHp domain of DesK, the C-terminal part of the ATP lid interacts with helix alpha1 of the DHp, through hydrogen bonds between His335 and Asp289 as well as Gly199 with Lys333, overview

conserved proline-222, which is adjacent to the phosphoryl acceptor histidine, contributes to helical bending, which is essential for the autokinase and phosphatase activities. The proline is essential for phosphatase activity. The C-terminal ends of the VicK dimer harbor two monomeric catalytic domains. The enzyme architecture with a signal transducer and sensor domain suggests a model where DHp helical bending and a CA swing movement are likely coordinated for autokinase activation, structure-function analysis, overview

the VicK kinase activates itself by helical bending of the DHp domain and coordinated swinging around of the catalytic and ATP binding domain to engage with the target histidine. Modelling of the active state structure of the catalytic ATP-binding domain and positioning of inactive domain. Structure-function analysis of the enzyme domains, detailed overview. Transient formation of the active site

basic architecture of VirA/VirG histidine kinase: the membrane-embedded VirA histidine kinase contains four modular domains, and the signal inputs activate the VirG response regulator. The sugar-binding protein ChvE interacts with the periplasmic domain, and phenols interact with the linker domain. The linker is predicted to adopt a GAF fold with the alpha1 helix. The conserved His474 is located in the dimerization domain of the kinase

the coordination and oxidation state of the sensor domain heme iron profoundly affect the enzyme's catalytic activity because they modulate its ATP binding affinity and thus change its kcat/Km(ATP) value. Effects of the response regulator and different divalent metal cations on the autophosphorylation reaction, overview

protein-protein docking analysis of the catalytic domain with the dimerization DHp domain of DesK, the C-terminal part of the ATP lid interacts with helix alpha1 of the DHp, through hydrogen bonds between His335 and Asp289 as well as Gly199 with Lys333, overview; the N-terminal transmembrane domain is dispensable but the PAS domain is needed for the kinase activity

the VicK kinase activates itself by helical bending of the DHp domain and coordinated swinging around of the catalytic and ATP binding domain to engage with the target histidine. Modelling of the active state structure of the catalytic ATP-binding domain and positioning of inactive domain. Structure-function analysis of the enzyme domains, detailed overview. Transient formation of the active site

conserved proline-222, which is adjacent to the phosphoryl acceptor histidine, contributes to helical bending, which is essential for the autokinase and phosphatase activities. The proline is essential for phosphatase activity. The C-terminal ends of the VicK dimer harbor two monomeric catalytic domains. The enzyme architecture with a signal transducer and sensor domain suggests a model where DHp helical bending and a CA swing movement are likely coordinated for autokinase activation, structure-function analysis, overview